Axon Guidance 3 Flashcards
What is the retinotectal projection pathway and why is it important
The route taken by retinal ganglion cell (RGC) axons from their source in the retina to their targets in the brain is probably the best studied projection pathway in the body, and provides an excellent example of how axon guidance cues co-operate to achieve accurate and topographical axon guidance
Where do the majority of retinotectal projection pathway axons terminate
Tectum - in fish
Superior colliculus - in mammals
What is the key site for the retinal axons
Lateral geniculate nucleus (LGN) in the thalmus
What is the role of the lateral geniculate nucleus
where post-synaptic axons relay retinal information to the primary visual cortex.
What is important about eye position in animals and the retinotectal projection pathway make-up
Non-mammals (frog) - lateral facing eyes with no crossover in visual field.
Mammals - forward-facing eyes so crossover in visual field.
Non-mammal pathways - retinal axon projections all cross to the other side of the head at the optic chiasm, so that all axons from the left eye project to the right side of the brain and those from the right eye all project to the left side of the brain.
Mammalian pathways - a proportion of axons from the mammalian ventrotemporal retina do not cross the chiasm but project ipsilaterally to the brain on the same side of the head. Thus each side of the brain receives visual information from both eyes.
How does ventrotemporal cross over produce better vision compared to the complete crossover of axon fibres shown in non-mammals
This provides mammals generally with better visual acuity, particularly in terms of perspective.
Explain the growth pattern of the retinotectal projection pathway
First they have to grow across the surface of the retina to the optic nerve head (ONH), at which point they turn away from the surface and extend out of the back of the ye into the optic nerve. This takes them to the ventral surface of the diencephalons where they enter the brain and negotiate the optic chiasm. They then grow along the optic tract to the tectum (or colliculus) where they terminate.
How do neighbouring RGCs interact
The RGCs have opposite but complementary terminal positions in the tectum/colliculus -
This means that a RGC immediately dorsal to another in the retina will project its axon to a position immediately ventral to it in the tectum
How do these RCG axons know the direct path to take
Brittis and silver 1995
Unknown but it’s been purposed that - a ring of inhibitory chondroitin sulphate proteoglycan (CSPG) recedes peripherally, starting just when the first retinal axons begin to extend just dorsal to the centre of the retina.
Neuroepithelial cells express axon promoting ECM molecules
(laminin) within this CSPG ring to continue to allow the RCGs to grow.
Later RGC axons may piggyback along the pioneer axons since they all express a number of different homophilic cell adhesion molecules, but the pathfinding mystery remains to be confirmed/discovered.
However, this phenomenon has only been observed in one study in the mouse and has not been found in other organisms, so many scientists are sceptical that such a mechanism exists
What was shown in mice that had undergone netrin knockout
WIDER READING - Deiner 1997
retinal axons have trouble growing through the Optic nerve head (ONH).
Resulting in a thinner optic nerve, due to fewer axons making it out of the eye.
Results in optic nerve hypoplasia. Shows taht DCC guides RCG axons out the optic disc locally rather than long range.
What has been shown in vitro regarding netrin and optic growth cones
In vitro, growth cone turning assays have shown that axons newly formed by retinal neurons are attracted to a netrin gradient, but it is not thought that netrin can diffuse far across the retinal surface, so it probably acts locally at the ONH.
What does laminin do to netrin and therefore growth cones
But netrin does not attract retinal axons in the presence of laminin; in fact, concentrated laminin induces growth cones to be repelled by netrin
Important - laminin is not inhibitory to axon growth, it just induces netrin to drop cAMP and prevent axon growth.
What does laminin do to cAMP
Prevents an increase in cAMP activity.
Where is laminin expressed
On the vitreal surface of the retina but not in the optic nerve head.
Why is laminin only present on the vitreal surface
Axons grow in presence of cAMP so stay away from vitreal surface and maintain on ONH.
It could also be the case, however, that the shape of the ONH, which essentially forms a hole at the back of the eye, means that there is only one way for axons to go, but that would not explain why so many axons do not grow through the ONH when the netrin gene is knocked out.
